S210: CAR T-CELLS ASSOCIATED ACUTE TOXICITY IN B-CELL NON-HODGKIN LYMPHOMA: REAL-WORLD STUDY FROM THE DESCAR-T REGISTRY
Authors: P. SESQUES, R. DI BLASI, S. LE GOUILL, G. CARTRON, G. MANSON, D. BEAUVAIS, F. LE BRAS, F. X. GROS, S. CHOQUET, P. BORIES, M. T. RUBIO, R. O. CASASNOVAS, L. BOUNAIX, M. MOHTY, M. JORIS, J. ABRAHAM, C. CASTILLA LLORENTE, M. LOSCHI, S. CARRAS, A. CHAUCHET, L. DRIEU LA ROCHELLE, J. ZERBIT, O. HERMINE, S. GUIDEZ, T. GASTINNE, J. J. TUDESQ, P. FOGARTY, F. BROUSSAIS, F. MORSCHHAUSER, R. HOUOT, C. THIEBLEMONT, E. BACHY
Journal: HemaSphere (2022)

Background: Cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) are common immune-related toxicities associated with chimeric antigen receptor (CAR)–T-cell therapy. Their clinical manifestations can be severe and potentially life threatening. Aims: Here, we report the French experience of CAR-T toxicity, we specifically addressed the modifiable risk factors for toxicity and we assessed management toxicity in real-world population. Methods: We conducted a study in a large cohort of R/R aggressive B-cell lymphoma patients (pts) treated with commercial products. All data were collected through the French DESCAR-T registry. CRS/ICANS were graded prospectively (ASTCT grade scale). Regarding previously validated predictive score of CRS and ICANS in the literature, EASIX score (LDHxCreatinine/Platelets), modified-EASIX score (m-EASIX: CRPxCreatinine/Platelets) and simplified-EASIX score (s-EASIX: LDH/Platelets) (Pennisi et al., 2021) were assessed in our cohort. Results: A total of 705 pts were included for the analysis of toxicity with a median follow-up of 12 months (range: 0.2-39). Notably, 74 pts (11%) pts had an ECOG/PS ≥ 2 before lymphodepletion. CRS of any grade occurred in 587 pts (83.3%) including 62 (10.5%) with grade 3 or higher (grade 3+). The median time from the infusion to the onset of CRS was 2 days (range: 0-34); the median time to resolution was 6 days (range: 1-30). ICANS of any grade occurred in 289 pts (41%) including 78 (27%) with grade 3+. The median time from the infusion to the onset was 6 days (range: 0-379); the median time to resolution was 7 days (range: 1-100). Most patients (94.5%) with ICANS had previously experienced CRS. Only 89 pts (29.9%) required admission to intensive care unit. Tocilizumab was the most common treatment for toxicity (411 pts, 68%) and 272 pts (45%) received corticosteroids. Interestingly, 38% of patients with CRS grade 1, 53 % with grade 2 and 65% with grade 3+ developed ICANS subsequently. In multivariate analysis, the parameters which retained statistical significance to predict any CRS were Axi-cel ([OR] = 2.79, 95% CI 1.75-4.45; p <0.0001) and elevated LDH (>upper limit normal; [OR] = 1.69, 95% CI 1.03-1.63; p = 0.03). Bulky mass > 5 cm ([OR] = 2.95, 95% CI 1.60-5.45; p = 0.0005), age <65 years ([OR] = 0.42, 95% CI 0.20-0.86; p = 0.01) and higher s-EASIX score ([OR] = 1.38, 95% CI 1.15-1.67; p = 0.0005) increased the risk of developing grade 3+ CRS. Parameters which retained statistical significance to predict any ICANS were Axi-cel ([OR] = 3.95, 95% CI 2.57-6.06; p <0.0001), ECOG ≥2 ([OR] = 2.10, 95% CI 1.26-3.51; p= 0.004), age ≥65 ([OR] = 3.17, 95% CI 2.10-4.79; p <0.0001) and higher s-EASIX score ([OR] = 1.20, 95% CI 1.03-1.40; p= 0.01). Axi-cel ([OR] = 13.1, 95% CI 3.98-43.3; p <0.001), ECOG ≥2 ([OR] = 0.04, 95% CI 1.007-4.38; p= 0.04) and higher s-EASIX score ([OR] = 1.35, 95% CI 1.08-1.67; p= 0.0067) increased the risk of developing grade 3+ ICANS. No survival impact (OS and PFS) was detected for pts who experimented any grade or grade 3+ of ICANS or CRS (Figure 1). Importantly, cumulative dose and duration of tocilizumab or corticosteroids were not significantly associated with adverse PFS or OS. Image:Summary/Conclusion: In this large study, robust biological and clinical predictive factors of CRS and ICANS were identified. A propensity-score matched comparison of axi-cel and tisa-cel for toxicities will be performed for the EHA congress. Neither grade 3+ CRS, ICANS, nor Tocilizumab or corticosteroids use for CAR-T toxicity had negative impact on survival.